Clinical Arrhythmias

LE ATION.

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The Role of Flecainide in the Management of Catecholaminergic Polymorphic Ventricular Tachycardia Krystien VV Lieve, 1 Arthur A Wilde, 1,2 Christian van der Werf 1 1. Heart Centre, Academic Medical Centre, Amsterdam, The Netherlands; 2. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia

Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but severe genetic cardiac arrhythmia disorder, with symptoms including syncope and sudden cardiac death due to polymorphic VT or ventricular fibrillation typically triggered by exercise or emotions in the absence of structural heart disease. The cornerstone of medical therapy for CPVT is β-blockers. However, recently flecainide has been added to the therapeutic arsenal for CPVT. In this review we summarise current data on the efficacy and role of flecainide in the treatment of CPVT.

Keywords Antiarrhythmic therapy, catecholaminergic ventricular tachycardia, flecainide, genetic, inherited channelopathies, sudden death Disclosure: The authors have no conflicts of interest to declare Acknowledgements: We acknowledge the support from The Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences (CVON 2010-12 PREDICT). Received: 9 January 2016 Accepted: 7 March 2016 Citation: Arrhythmia & Electrophysiology Review 2016;5(1):45–9 Access at: www.AERjournal.com DOI: 10.15420/AER.2016.3.3 Correspondence: Christian van der Werf, Department of Cardiology, Academic Medical Centre, PO Box 22660, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail: [email protected]

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but severe genetic cardiac arrhythmia disorder. Clinically, CPVT most often presents in childhood with symptoms such as syncope or sudden cardiac death due to polymorphic ventricular tachycardia (VT) or ventricular fibrillation typically triggered by exercise or emotions in the absence of structural heart disease.1 Mutations in the RYR2 gene, which encodes the cardiac ryanodine receptor calcium release channel (RyR2), can be identified in the vast majority of the CPVT cases and follow an autosomal dominant inheritance pattern,2 whereas a small percentage of cases are due to homozygous or compound heterozygous mutations in the gene encoding cardiac calsequestrin (CASQ2).3 Both RyR2 and CASQ2 are involved in intracellular calcium homeostasis in the cardiomyocyte. Mutations in these genes mainly cause diastolic calcium leakage from the sarcoplasmatic reticulum through the RyR2 receptor, eventually resulting in delayed afterdepolarisations and triggered activity, which is most pronounced during states of sympathetic activation.4 Other genes that have been discovered and only represent a small percentage of CPVT cases are TRDN (encoding triadin) and CALM1 (encoding calmodulin).5,6 Mutations in the CALM2 gene have been associated with overlapping features of the congenital long-QT syndrome and CPVT.7 A yet-to-be-identified gene on chromosome 7p14–p22 has been linked to a highly malignant autosomal recessive form of CPVT. This phenotype is characterised by exercise-induced ventricular arrhythmia, and patients have a minor QT prolongation.8 Approximately 40  % of the CPVT cases remain mutation negative.9,10

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Untreated, CPVT has a high mortality rate of up to 30  % among individuals with the classic phenotype who are aged 25 %, flecainide dosing should be decreased or discontinued. It is, however, reassuring that in the published reports a proarrhythmic effect of flecainide has not been observed in patients with CPVT. Furthermore, data accumulated over the past 27 years indicate that flecainide is safe to use in carefully selected patients without structural heart disease.32 Additionally, long-term (27–29 years) follow-up data have been reported for two patients with CPVT patients on flecainide.23,25

Conclusion Preliminary results with flecainide in patients with CPVT are encouraging. However, a larger study with long-term follow-up is needed to fully elucidate the efficacy of flecainide, in particular its ability to prevent cardiac events in the long term. n

Hayashi M, Denjoy I, Extramiana F, et al. Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia. Circulation 2009;119:2426–34. DOI: 10.1161/ CIRCULATIONAHA.108.829267; PMID: 19398665. Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, et al. The RYR2encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: a comprehensive open reading frame mutation analysis. J Am Coll Cardiol 2009;54:2065–74. DOI: 10.1016/j.jacc.2009.08.022; PMID: 19926015. Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002;106:69–74. PMID: 12093772. Coumel P, Fidelle J, Lucet V, et al. Catecholamine-induced severe ventricular arrhythmias with Adam-Stokes in children: report of four cases. Br Heart J 1978;40:28–37. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932–63. DOI: 10.1016/j.hrthm.2013.05.014; PMID: 24011539. Roston TM, Vinocur JM, Maginot KR, et al. Catecholaminergic polymorphic ventricular tachycardia in children: analysis of therapeutic strategies and outcomes from an international multicenter registry. Circ Arrhythm Electrophysiol 2015;8:633–42. DOI: 10.1161/CIRCEP.114.002217; PMID: 25713214. Watanabe H, Chopra N, Laver D, et al. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in

16.

17. 18.

19.

20.

21.

22.

23.

mice and humans. Nat Med 2009;15:380–3. DOI: 10.1038/ nm.1942; PMID: 19330009. Holmes B, Heel RC. Flecainide. A preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1985;29:1–33. PMID: 3882390. Roden DM, Woosley RL. Drug therapy. Flecainide. N Engl J Med 1986;315:36–41. PMID: 3520324. Bannister ML, Thomas NL, Sikkel MB, et al. The mechanism of flecainide action in CPVT does not involve a direct effect on RyR2. Circ Res 2015;116:1324–35. DOI: 10.1161/ CIRCRESAHA.116.305347; PMID: 25648700. Liu N, Denegri M, Ruan Y, et al. Short communication: flecainide exerts an antiarrhythmic effect in a mouse model of catecholaminergic polymorphic ventricular tachycardia by increasing the threshold for triggered activity. Circ Res 2011;109:291–5. DOI: 10.1161/CIRCRESAHA.111.247338; PMID: 21680895. Sikkel MB, Collins TP, Rowlands C, et al. Flecainide reduces Ca(2+) spark and wave frequency via inhibition of the sarcolemmal sodium current. Cardiovasc Res 2013;98:286–96. DOI: 10.1093/cvr/cvt012; PMID: 23334259. Smith GL, MacQuaide N. The direct actions of flecainide on the human cardiac ryanodine receptor: keeping open the debate on the mechanism of action of local anesthetics in CPVT. Circ Res 2015;116:1284–6. DOI: 10.1161/ CIRCRESAHA.115.306298; PMID: 25858058. Hwang HS, Hasdemir C, Laver D, et al. Inhibition of cardiac Ca2+ release channels (RyR2) determines efficacy of class I antiarrhythmic drugs in catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol 2011;4:128– 35. DOI: 10.1161/CIRCEP.110.959916; PMID: 21270101. van der Werf C, Kannankeril PJ, Sacher F, et al. Flecainide therapy reduces exercise-induced ventricular arrhythmias

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Flecainide in Catecholaminergic Polymorphic Ventricular Tachycardia

24.

25.

26.

27.

28.

29.

in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol 2011;57:2244–54. DOI: 10.1016/j.jacc.2011.01.026; PMID: 21616285. Khoury A, Marai I, Suleiman M, et al. Flecainide therapy suppresses exercise-induced ventricular arrhythmias in patients with CASQ2-associated catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2013;10:1671–5. DOI: 10.1016/j.hrthm.2013.08.011; PMID: 23954267. Watanabe H, van der Werf C, Roses-Noguer F, et al. Effects of flecainide on exercise-induced ventricular arrhythmias and recurrences in genotype-negative patients with catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2013;10:542–7. DOI: 10.1016/j. hrthm.2012.12.035; PMID: 23286974. Padfield GJ, AlAhmari L, Lieve KV et al. Flecainide monotherapy is an option for selected patients with catecholaminergic polymorphic ventricular tachycardia intolerant of β-blockade. Heart Rhythm 2016;13:609–13. DOI: 10.1016/j.hrthm.2015.09.027; PMID: 26416620. De Ferrari GM, Dusi V, Spazzolini C, et al. Clinical management of catecholaminergic polymorphic ventricular tachycardia: the role of left cardiac sympathetic denervation. Circulation 2015;131:2185–93. DOI: 10.1161/ CIRCULATIONAHA.115.015731; PMID: 26019152. Leren IS, Saberniak J, Majid E, et al. Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2016;13:433–40. DOI: 10.1016/j.hrthm.2015.09.029; PMID: 26432584. Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. 2015

ARRHYTHMIA & ELECTROPHYSIOLOGY REVIEW

Van Der Werf_FINAL.indd 49

30.

31.

32.

33.

34.

35.

ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the Europe. Eur Heart J 2015;36:2793–867. DOI: 10.1093/eurheartj/ehv316; PMID: 26320108. Hayashi M, Denjoy I, Extramiana F, et al. The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands. Europace 2012;14:1344–51. DOI: 10.1093/europace/eus031; PMID: 22383456. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991;324:781–8. PMID: 1900101. Aliot E, Capucci A, Crijns HJ, et al. Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation. Europace 2011;13:161–73. DOI: 10.1093/ europace/euq382; PMID: 21138930. Biernacka EK, Hoffman P. Efficacy of flecainide in a patient with catecholaminergic polymorphic ventricular tachycardia. Europace 2011;13:129–30. DOI: 10.1093/europace/euq279; PMID: 20798117. Pott C, Dechering DG, Reinke F, et al. Successful treatment of catecholaminergic polymorphic ventricular tachycardia with flecainide: a case report and review of the current literature. Europace 2011;13:897–901. DOI: 10.1093/europace/euq517; PMID: 21292648. Sy RW, Gollob MH, Klein GJ, et al. Arrhythmia characterization and long-term outcomes in catecholaminergic polymorphic

ventricular tachycardia. Heart Rhythm 2011;8:864–71. DOI: 10.1016/j.hrthm.2011.01.048; PMID: 21315846. 36. Hong RA, Rivera KK, Jittirat A, et al. Flecainide suppresses defibrillator-induced storming in catecholaminergic polymorphic ventricular tachycardia. Pacing Clin Electrophysiol 2012;35:794–7. DOI: 10.1111/j.1540-8159.2012.03421.x; PMID: 22553997. 37. Jacquemart C, Ould Abderrahmane F, Massin MM. Effects of flecainide therapy on inappropriate shocks and arrhythmias in catecholaminergic polymorphic ventricular tachycardia. J Electrocardiol 2012;45:736–8. DOI: 10.1016/j. jelectrocard.2012.05.002; PMID: 22672791. 38. Mantziari L, Vassilikos V, Anastasakis A, et al. A de novo novel cardiac ryanodine mutation (Ser4155Tyr) associated with catecholaminergic polymorphic ventricular tachycardia. Ann Noninvasive Electrocardiol 2013; 18:571–6. DOI: 10.1111/ anec.12089; PMID: 24147812. 39. Wangüemert-Pérez F, Ruiz-Hernández PM, Campuzano O, et al. Flecainide in patient with aggressive catecholaminergic polymorphic ventricular tachycardia due to novel RYR2 mutation. Minerva Cardioangiol 2014;62:363–6. PMID: 25012103. 40. Miyake CY, Webster G, Czosek RJ, et al. Efficacy of implantable cardioverter defibrillators in young patients with catecholaminergic polymorphic ventricular tachycardia: success depends on substrate. Circ Arrhythm Electrophysiol 2013;6:579–87. DOI: 10.1161/CIRCEP.113.000170; PMID: 23667268. 41. Roses-Noguer F, Jarman JW, Clague JR, et al. Outcomes of defibrillator therapy in catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm 2014;11:58–66. DOI: 10.1016/j.hrthm.2013.10.027; PMID: 24120999.

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The Role of Flecainide in the Management of Catecholaminergic Polymorphic Ventricular Tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but severe genetic cardiac arrhythmia disorder, with symptoms including syncope...
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